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Mammary tumour cells remodel the bone marrow vascular microenvironment to support metastasis
- Source :
- Nature Communications, Nature Communications, Vol 12, Iss 1, Pp 1-17 (2021)
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group UK, 2021.
-
Abstract
- Bone marrow is a preferred metastatic site for multiple solid tumours and is associated with poor prognosis and significant morbidity. Accumulating evidence indicates that cancer cells colonise specialised niches within the bone marrow to support their long-term propagation, but the precise location and mechanisms that mediate niche interactions are unknown. Using breast cancer as a model of solid tumour metastasis to the bone marrow, we applied large-scale quantitative three-dimensional imaging to characterise temporal changes in the bone marrow microenvironment during disease progression. We show that mouse mammary tumour cells preferentially home to a pre-existing metaphyseal domain enriched for type H vessels. Metastatic lesion outgrowth rapidly remodelled the local vasculature through extensive sprouting to establish a tumour-supportive microenvironment. The evolution of this tumour microenvironment reflects direct remodelling of the vascular endothelium through tumour-derived granulocyte-colony stimulating factor (G-CSF) in a hematopoietic cell-independent manner. Therapeutic targeting of the metastatic niche by blocking G-CSF receptor inhibited pathological blood vessel remodelling and reduced bone metastasis burden. These findings elucidate a mechanism of ‘host’ microenvironment hijacking by mammary tumour cells to subvert the local microvasculature to form a specialised, pro-tumorigenic niche.<br />The visualisation of the bone metastasis process in a spatial temporal manner is lacking. Here, the authors use three-dimensional quantitative imaging and show that mouse mammary tumour cells preferentially home to endothelial subtype type H vessels within the bone marrow and remodel this vasculature by producing granulocyte-colony stimulating factor.
- Subjects :
- Science
General Physics and Astronomy
Bone Neoplasms
Breast Neoplasms
Mammary Neoplasms, Animal
Biology
Cellular imaging
General Biochemistry, Genetics and Molecular Biology
Article
Bone and Bones
Metastasis
Mice
Breast cancer
Imaging, Three-Dimensional
Bone Marrow
Granulocyte Colony-Stimulating Factor
Receptors, Colony-Stimulating Factor
medicine
Tumor Microenvironment
Animals
Humans
Neoplasm Metastasis
Receptor
Multidisciplinary
Bone metastasis
Neoplasms, Second Primary
General Chemistry
medicine.disease
Haematopoiesis
medicine.anatomical_structure
Cancer cell
Cancer research
Disease Progression
Bone marrow
Blood vessel
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....ca6d342dc17b7ada09e2480790a62fba